In studies using co-cultures of mouse myocardial cells and rat ovarian granulosa cells we have demonstrated that interceullular communication is established between the heterologous cells and that information regarding hormone stimulation can be transmitted from one cell type to the other via a contact dependent, presumably gap junctional, mechanism. Specifically, exposure of the co-cultures to hormones which stimulate one cell type results in the response of both. From these studies it appears that a "communicator" of hormonal stimulation is transmitted between the cells. The chemical nature of this substance is not known, however, the results which have been obtained are consistent with the hypothesis that it is cAMP. In order to determine whether similar events occur between heterologous cells in vivo, cell to cell communication has been examined in the cumulus-oocyte complex of the rat. These studies show that the cells are ionically coupled and are able to transmit low molecular weight dyes until a few hours before ovulation. At this time, coincident with the resumption of oocyte maturation, communication is interrupted. In order to examine the extent to which the termination of communication is causally related to the regulation of oocyte development, studies using an in vitro system have been initiated. These investigations suggest the possibility that cAMP may be transmitted from the cumulus to maintain developmental arrest in the oocyte and that the interruption of communication terminates its supply of nucleotide. In the absence of cAMP the oocyte matures. Taken together these findings suggest that the intercellular communication of low molecular weight modulators of cell function may represent a mechanism for the control of differentiation and development that has previously gone unrecognized. Experiments to test this proposition will be conducted in the coming year.